We propose to develop 'magnetomicelles' for the triggered release of hydrophobic pharmaceuticals either from the bloodstream or an injected gel at a particular location in the body. Monodisperse magnetic nanoparticles with high magnetocrystalline anisotropies will be encapsulated within crosslinked polyacrylate-PEO 'stealth' micelles, along with hydrophobic drugs. The encapsulated pharmaceuticals will then be released from these micelles in response to an external radiofrequency (RF) magnetic field supplied by an induction coil. The applied field will induce oscillating relaxation of the particles' magnetic moments, which will locally heat the magnetic particles. Thermal energy will be transported to the micellar shell, which will accelerate the diffusion of co-encapsulated, hydrophobic molecules from the glassy micellar core. Because subdomain magnetic particles can be excited with kHz frequencies and low field amplitudes, this technique will specifically heat the particles and not surrounding tissue. In principle, both the release period and amount of drug released could be controlled by the intensity and duration of the applied RF field. We anticipate that these composite micelles can act as biocompatible, latent reservoirs that can stably retain drugs in biological hosts for long periods of time until the moment the drugs are needed, when they can be released almost instantaneously. In the proposed R21 research, we will demonstrate the principle of magnetomicelle drug carriers; we hope that successful proof of principle will lead to further (R01- funded) research on the use of these vehicles in vivo.
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